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瘦素对早产儿脑白质损伤模型大鼠远期空间记忆能力的影响
Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain
目的 通过观察瘦素对早产儿脑白质损伤模型大鼠空间记忆的影响，探索其神经保护作用。方法 将80只新生大鼠随机分为假手术组（n=27）、模型组（n=27）和瘦素干预组（n=26），模型组和瘦素干预组大鼠制备早产儿脑白质损伤模型，瘦素干预组于造模后立即给予生理盐水稀释的瘦素（100 μg/kg），连续4 d。观察各组大鼠存活情况并监测体重变化，21日龄后通过Morris水迷宫实验观察各组大鼠空间记忆能力。结果 各组新生大鼠存活率比较差异无统计学意义（P > 0.05）。至生后10 d内，瘦素干预组大鼠体重接近假手术组，但低于模型组（P < 0.05）；10 d后瘦素干预组生长速度加快，体重超过模型组和假手术组，但差异无统计学意义（P > 0.05）。定位航行训练结果显示：实验第2天开始，各组平台潜伏期比较差异有统计学意义（P < 0.05）；从第4天开始，瘦素干预组平台潜伏期接近假手术组，短于模型组（P < 0.05）。空间搜索实验结果显示：与假手术组比较，模型组穿越平台次数减少，平台潜伏期延长（P < 0.05）；与模型组比较，瘦素干预组穿越平台次数增加，平台潜伏期缩短（P < 0.05），且与假手术组比较差异均无统计学意义（P > 0.05）。结论 瘦素干预可以减轻早产儿脑白质损伤的空间记忆障碍，对早产儿脑损伤具有神经保护作用，值得进一步研究。
Objective To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. Methods A total of 80 neonatal rats were randomly divided into 3 groups:sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. Results There was no significant difference in the survival rate of rats between the three groups (P > 0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P < 0.05); more than 10 days after birth, the leptin intervention group had rapid growth with higher body weight than the model and sham-operation groups (P > 0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (P < 0.05); from the fourth day of experiment, the leptin intervention group had a similar latency period as the sham-operation and a significantly shorter latency period than the model group (P < 0.05). The results of space search experiment showed that compared with the sham-operation group, the model group had a significant reduction in the number of platform crossings and a significantly longer latency period (P < 0.05); compared with the model group, the leptin intervention group had a significantly increased number of platform crossings and a significantly shortened latency period (P < 0.05), while there was no significant difference between the leptin intervention and sham-operation groups. Conclusions Leptin can alleviate spatial memory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.
[1] World Health Organization. Preterm birth Fact sheet no 363. WHO[EB/OL]. (2017-11). http://www.who.int//mediacentre/factsheets/fs363/en/.
[2] Burns YR, Danks M, O'Callaghan MJ, et al. Motor coordination difficulties and physical fitness of extremely-low-birthweight children[J]. Dev Med Child Neurol, 2009, 51(2):136-142.
[3] Woodward LJ, Edgin JO, Thompson D, et al. Object working memory deficits predicted by early brain injury and development in the preterm infant[J]. Brain, 2005, 128(Pt 11):2578-2587.
[4] Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia[J]. J Neurosci, 2002, 22(2):455-463.
[5] Volpe JJ. Brain injury in premature infants:a complex amalgam of destructive and developmental disturbances[J]. Lancet Neurol, 2009, 8(1):110-124.
[6] du Plessis AJ. Neurology of the newborn infant. Preface[J]. Clin Perinatol, 2009, 36(4):xi-xiii.
[7] Oomura Y, Hori N, Shiraishi T, et al. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK Ⅱ phosphorylation in rats[J]. Peptides, 2006, 27(11):2738-2749.
[8] 朱丽华, 蒋犁, 张志华, 等. 缺氧缺血致低龄大鼠脑白质损伤和神经功能障碍的实验研究[J]. 临床儿科杂志, 2007, 25(9):784-787.
[9] Favaro A, Santonastaso P, Manara R, et al. Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa[J]. Biol Psychiatry, 2012, 72(10):864-870.
[10] Koyama KI, Asakawa A, Nakahara T, et al. Intelligence quotient and cognitive functions in severe restricting-type anorexia nervosa before and after weight gain[J]. Nutrition, 2012, 28(11-12):1132-1136.
[11] Sternheim L, Startup H, Pretorius N, et al. An experimental exploration of social problem solving and its associated processes in anorexia nervosa[J]. Psychiatry Res, 2012, 200(2-3):524-529.
[12] Johnston JM, Hu WT, Fardo DW, et al. Low plasma leptin in cognitively impaired ADNI subjects:gender differences and diagnostic and therapeutic potential[J]. Curr Alzheimer Res, 2014, 11(2):165-174.
[13] Guimond D, Diabira D, Porcher C, et al. Leptin potentiates GABAergic synaptic transmission in the developing rodent hippocampus[J]. Front Cell Neurosci, 2014, 8:235.
[14] Durakoglugil M, Irving AJ, Harvey J. Leptin induces a novel form of NMDA receptor-dependent long-term depression[J]. J Neurochem, 2005, 95(2):396-405.
[15] Shanley LJ, Irving AJ, Harvey J. Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity[J]. J Neurosci, 2001, 21(24):RC186.
[16] Shanley LJ, Irving AJ, Rae MG, et al. Leptin inhibits rat hippocampal neurons via activation of large conductance calcium-activated K+ channels[J]. Nat Neurosci, 2002, 5(4):299-300.
[17] O'Malley D, Irving AJ, Harvey J. Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels[J]. FASEB J, 2005, 19(13):1917-1919.
[18] Walker CD, Long H, Williams S, et al. Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunits[J]. J Neurosci Res, 2007, 85(4):816-828.
[19] Irving AJ, Wallace L, Durakoglugil D, et al. Leptin enhances NR2B-mediated N-methyl-D-aspartate responses via a mitogen-activated protein kinase-dependent process in cerebellar granule cells[J]. Neuroscience, 2006, 138(4):1137-1148.
[20] Nagasaki H, Ohta T. Extra-uterine growth and adipocytokines in appropriate-for-gestational-age preterm infants[J]. Pediatr Int, 2015, 58(7):584-588.
[21] Veselá PK, Kaniok R, Bayer M. Markers of bone metabolism, serum leptin levels and bone mineral density in preterm babies[J]. J Pediatr Endocrinol Metab, 2016, 29(1):27-32.
[22] Okuma C, Hernández MI, Rodríguez P, et al. Microstructural brain and multivoxel spectroscopy in very low birth weight infants related to insulin-like growth factor concentration and early growth[J]. Horm Res Paediatr, 2013, 79(4):197-207.
[23] Mela V, Díaz F, Borcel E, et al. Long term hippocampal and cortical changes induced by maternal deprivation and neonatal leptin treatment in male and female rats[J]. PLoS One, 2015, 10(9):e0137283.
国家自然科学基金（81771628）。
